Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis

  title={Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis},
  author={Emily Pisha and Hee-byung Chai and Ik-Soo Lee and Tangai E. Chagwedera and N. R. Farnsworth and Geoffrey A. Cordell and Chris Beecher and Harry H. S. Fong and A. Douglas Kinghorn and Daniel M. Brown and Mansukh C. Wani and Monroe E. Wall and Tina J Hieken and Tapas K. Das Gupta and John M. Pezzuto},
  journal={Nature Medicine},
As a result of bioassay–guided fractionation, betulinic acid, a pentacyclic triterpene, was identified as a melanoma–specific cytotoxic agent. In follow–up studies conducted with athymic mice carrying human melanomas, tumour growth was completely inhibited without toxicity. As judged by a variety of cellular responses, antitumour activity was mediated by the induction of apoptosis. Betulinic acid is inexpensive and available in abundant supply from common natural sources, notably the bark of… 

Betulinic Acid for Cancer Treatment and Prevention

  • S. Fulda
  • Biology, Chemistry
    International journal of molecular sciences
  • 2008
Compounds that exert a direct action on mitochondria present promising experimental cancer therapeutics, since they may trigger cell death under circumstances in which standard chemotherapeutics fail.

Lupane Triterpenoids—Betulin and Betulinic acid derivatives induce apoptosis in tumor cells

Investigating derivatives exerted a dose dependent antiproliferative action at micromolar concentrations toward target tumor cell lines induced apoptosis and the appearance of a typical ladder pattern in the DNA fragmentation assay.

Targeting mitochondrial apoptosis by betulinic acid in human cancers.

Development of C-20 modified betulinic acid derivatives as antitumor agents.

Betulinic acid, a natural compound with potent anticancer effects

In-vitro studies have identified this agent as potently effective against a wide variety of cancer cells, also those derived from therapy-resistant and refractory tumors, whereas it has been found to be relatively nontoxic for healthy cells.

Synthesis of betulinic acid derivatives with activity against human melanoma.

Betulinic acid: a natural product with anticancer activity.

  • S. Fulda
  • Biology, Chemistry
    Molecular nutrition & food research
  • 2009
In contrast to the potent cytotoxicity of BA against a variety of cancer types, nonmalignant cells and normal tissue remained relatively resistant to BA, indicating a therapeutic window.

Betulinic acid inhibits prostate cancer growth through inhibition of specificity protein transcription factors.

It is shown that betulinic acid decreases expression of vascular endothelial growth (VEGF) and the antiapoptotic protein survivin and acts as a novel anticancer agent through targeted degradation of Sp proteins that are highly overexpressed in tumors.



Tumor inhibitors. I. Preliminary investigation of antitumor activity of Sarracenia flava.

The chloroform and aqueous extracts of the roots of Sarracenia flava showed antitumor activity against human epidermoid carcinoma of the nasopharynx (KB). Betulin was identified as one constituent

Anti-AIDS agents, 11. Betulinic acid and platanic acid as anti-HIV principles from Syzigium claviflorum, and the anti-HIV activity of structurally related triterpenoids.

Evaluation of anti-HIV activity with eight derivatives of 1 revealed that dihydrobetulinic acid was also a potent inhibitor of HIV replication, and there was no apparent correlation between anti-hIV activity and the inhibition of PKC among these compounds.

Tumor inhibitory agents from Vauquelinia corymbosa (Rosaceae).

The chloroform extract of Vauquelinia corymbosa Correa has shown activity against the P-388 lymphocytic leukemia test system. The constituents responsible for this activity were identified as uvaol,

Tumor-inhibitory agent from Hyptis emoryi (Labiatae).

The extract of Hyptis emoryi (Labiatae) has shown tumor-inhibiting properties in the 5WA16 test system of the Cancer Chemotherapy National Service Center and the agent responsible for this action was shown to be betulinic acid.

Apoptosis in the genesis and prevention of cancer.

  • H. ThompsonR. StrangeP. Schedin
  • Biology, Medicine
    Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
  • 1992
It is essential to consider the role of cell loss in the tumorigenic process and the hypothesis that misregulation of apoptosis results in a failure of tissue size regulation that contributes to the development of cancer.

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Comparison of the alkaloid content of S. pierrei and Stephania erecta strongly suggested separate identities for the two plants, and cytotoxic and antimalarial activity was found.

Sequential chemoimmunotherapy in the treatment of metastatic melanoma.

Cytotoxic chemotherapy can be administered safely immediately before or immediately after IL-2 and alpha IFN and cutaneous depigmentation induced by this treatment suggests that immune modulation may contribute to the antimelanoma effect of this treatment.

The biology of cell death in tumours.

Evidence is presented for the numerical and biological importance of cell death in tumour growth and regression and for the control of these endogenous mechanisms for effecting cell death, which could lead to powerful new means of controlling the growth of tumours.

Tamoxifen: is it useful in the treatment of patients with metastatic melanoma?

  • E. McClayM. E. Mcclay
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 1994
While TAM as a single agent is minimally active in treating patients with metastatic melanoma, when it is combined with DTIC, BCNU, and DDP, a marked improvement in the overall response rate is observed.